Interleukin-6 inhibition: a therapeutic strategy for the management of adult-onset Still’s disease

ABSTRACT

Introduction

Patients with adult-onset Still’s disease have markedly elevated serum levels of proinflammatory cytokines, such as IL-1β, IL-6, and IL-18, suggesting the potential of these molecules as therapeutic targets. IL-6 accelerates macrophage and cytotoxic T-cell differentiation and neutrophil and macrophage chemotaxis and is one of the most important cytokines in the pathogenesis of adult-onset Still’s disease.

Areas covered

The review summarizes the importance of IL-6 in the pathogenesis of adult-onset Still’s disease and clinical aspects of IL-6 inhibition from retrospective and prospective studies.

Expert opinion

Adult-onset Still’s disease is a systemic inflammatory disease of unknown etiology and characterized by elevated various proinflammatory cytokines. In particular, serum concentrations of IL-6 is significantly high in patients with active adult-onset Still’s disease, and many case reports, cohort studies and one randomized, placebo-controlled trail have shown the efficacy of IL-6 blockade in patients with adult-onset Still’s disease who were refractory to glucocorticoids and other immunosuppressive treatments. IL-6 inhibition is effective for both systemic and joint manifestations with arthritis improving slowly. There is still a concern over the triggering of macrophage activation syndrome; however, the IL-6 inhibition strategy has introduced better management of adult-onset Still’s disease.

KEYWORDS:

• Interleukin-6
• adult-onset Still’s disease
• tocilizumab

Article highlights

• Adult-onset Still’s disease is a systemic inflammatory disease of unknown etiology and characterized by various inflammatory symptoms such as fever, rash, and arthritis.

• Chemokines and proinflammatory cytokines play a pivotal role in the pathogenesis of adult-onset Still’s disease.

• IL-6 accelerates the differentiation of macrophages and cytotoxic T cells and the chemotaxis of neutrophils and macrophages. It is one of markedly elevated proinflammatory cytokines in patients with adult-onset Still’s disease.

• IL-6 inhibition has been proved to be useful in the management of adult-onset Still’s disease refractory to glucocorticoids and conventional immunosuppressive drugs to achieve sustained remission and reduce the risk of relapses and life-threatening complications.

• Tocilizumab, an anti-IL-6 receptor inhibitor, is effective for both systemic and joint manifestations as well as for severe life-threatening manifestations.

• The safety profile of tocilizumab in adult-onset Still’s disease has no new signal. However, attention is needed to macrophage activation syndrome after tocilizumab initiation and anaphylaxis reaction to tocilizumab.

Declaration of interest

Y Kaneko and T Takeuchi have received grants and speaking fees from Chugai, Eli Lilly, Novartis, Pfizer, Sanofi, and Asahi Kasei. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

The authors have no funding to report.